Blunted reward-related activation to food scenes distinguishes individuals with alcohol use disorder in a pilot case-control fMRI pilot study.

BACKGROUND: Alcohol use disorder (AUD) is thought to bias the neurocircuitry underlying reward processing and motivation to preferentially attend to conditioned alcohol cues over natural rewards. The present case-control pilot study evaluated this hypothesis using novel natural reward paradigms. METHODS: Twenty-eight participants (AUD, n = 14, light drinkers, n = 14) were recruited-AUD participants reported 44.0% heavy drinking days (%HDD) and 4.67 drinks/day over the preceding 90 days. Functional magnetic resonance imaging (fMRI) data were acquired during the administration of three separate picture-viewing paradigms of alcohol cues, food scenes, and social reward, respectively. Independent samples t-tests were performed to compare groups' fMRI data and exploratory correlation analyses were performed to examine associations with clinical characteristics of AUD. RESULTS: Food scenes elicited abnormally low reward-related activation, within the superior frontal gyrus and caudate bilaterally, among AUD participants. Lower activation to food scenes within the superior frontal gyrus was, in turn, associated with higher levels of past-month %HDD among AUD participants, specifically, along with craving and alcohol dependence severity when examined across the full sample. Contrasting reward types (e.g., alcohol cues vs. food scenes) did not reveal "preferential" activation to differentiate groups. CONCLUSIONS: Heavy drinking appears associated with reduced responsivity to natural rewards, specifically food rather than social cues. Neural mechanisms underlying the high prevalence of malnutrition among individuals with AUD may involve some combination of blunted approach-related affect and reduced craving-related motivation to eat when food is present, resulting in limited engagement of cortico-striato-thalamic motor circuitry supporting food acquisition. However, given the preliminary nature of this pilot study, such formulations remain tentative until larger follow-up studies can be conducted. From a potential translational standpoint, the ability of promising therapeutics to demonstrate increased responsivity to natural rewards, specifically nutritive reward may serve as a valuable complementary efficacy indicator for future clinical neuroimaging trials in AUD.

Leveraging meta-regression to test if medication effects on cue-induced craving are associated with clinical efficacy.

RATIONALE: The alcohol cue exposure paradigm is a common method for evaluating new treatments for alcohol use disorder (AUD); however, it is unclear if medication-related reductions in cue-induced craving in the human laboratory can predict the clinical success of those medications in reducing alcohol consumption during clinical trials. OBJECTIVES: To use a novel meta-analytic approach to test whether medication effect sizes on cue-induced alcohol craving are associated with clinical efficacy in clinical trials. METHOD: We searched the literature for medications tested for AUD treatment using both the alcohol cue-reactivity paradigm and randomized clinical trials (RCTs). For alcohol cue-reactivity studies, we computed medication effect sizes for cue-induced alcohol craving (k = 36 studies, 15 medications). For RCTs, we calculated medication effect sizes for heavy drinking and abstinence (k = 139 studies, 19 medications). Using medication as the unit of analysis, we applied the Williamson-York bivariate weighted least squares estimation to account for errors in both independent and dependent variables. We also conducted leave-one-out cross validation simulations to examine the predictive utility of cue-craving medication effect sizes on RCT heavy drinking and abstinence endpoints. RESULTS: There was no significant relationship between medication effects on cue-induced alcohol craving in the human laboratory and medication effects on heavy drinking ( ß ^ = 0.253, SE = 0.189, p = 0.090) and abstinence ( ß ^ = 0.829, SE = 0.747, p = 0.133) in RCTs. CONCLUSIONS: The preliminary results of the current study challenge the assumption that alcohol cue-reactivity alone can be used as an early efficacy indicator for AUD pharmacotherapy development. These findings suggest that a wider range of early efficacy indicators and experimental paradigms be considered for Phase II testing of novel compounds.

Multi-modal neuroimaging reveals differences in alcohol-cue reactivity but not neurometabolite concentrations in adolescents who drink alcohol.

BACKGROUND: The objective of this multi-modal neuroimaging study was to identify neuroscience-informed treatment targets for adolescent alcohol use disorder (AUD) by examining potential neural alterations associated with adolescent alcohol use. METHODS: Adolescents (ages 17-19) who heavily used (n=49) or did not use alcohol (n=22) were recruited for a multi-modal neuroimaging protocol, including proton magnetic resonance spectroscopy within the dorsal anterior cingulate cortex (dACC) and an fMRI alcohol cue-reactivity task. The alcohol cue-reactivity task was analyzed across 11 a priori regions-of-interest (ROI), including the dACC, and in an exploratory whole-brain approach. Correlations were run between neurometabolite levels and alcohol cue-reactivity in the dACC. RESULTS: There were no significant group differences in absolute neurometabolite concentrations. Compared to the control group, the alcohol-using group exhibited heightened alcohol cue reactivity in the left amygdala ROI (p=0.04). The whole-brain approach identified higher alcohol cue reactivity in the alcohol-using group compared to controls in the amygdala and occipital regions, and lower reactivity in the parietal lobe. Whole-brain sex effects were noted, with females displaying higher reactivity regardless of group. No significant correlations were found between neurometabolite levels and alcohol cue-reactivity in the dACC. CONCLUSIONS: The null neurometabolic findings may be due to age, relatively low severity of alcohol use, and non-treatment-seeking status of the participants. Females showed overall higher reactivity to alcohol cues, indicating a sex effect regardless of alcohol use history. Higher amygdala reactivity in alcohol-using adolescents suggests that emotional processing related to alcohol cues may be a useful target for future adolescent AUD interventions.

The effects of age on the severity of problem drinking: Mediating effects of positive alcohol expectancy and neural correlates.

Aging is associated with reduction in the severity of alcohol misuse. However, the psychological and neural mechanisms underlying the age-related changes remain unclear. Here, we tested the hypothesis that age-related diminution of positive alcohol expectancy (AE) mediated the effects of age on problem drinking and investigated the neural correlates of the mediating effects. Ninety-six drinkers 21-85 years of age, including social drinkers and those with mild/moderate alcohol use disorder (AUD), were assessed for global positive (GP) AE and problem drinking, each with the Alcohol Expectancy Questionnaire and Alcohol Use Disorders Identification Test (AUDIT), and with brain imaging during alcohol cue exposure. We processed imaging data with published routines; identified the correlates shared between whole-brain regression against age, GP and AUDIT scores; and performed mediation and path analyses to explore the interrelationships between the clinical and neural variables. The results showed that age was negatively correlated with both GP and AUDIT scores, with GP score completely mediating the correlation between age and AUDIT score. Lower age and higher GP correlated with shared cue responses in bilateral parahippocampal gyrus and left middle occipital cortex (PHG/OC). Further, higher GP and AUDIT scores were associated with shared cue responses in bilateral rostral anterior cingulate cortex and caudate head (ACC/caudate). Path analyses demonstrated models with significant statistical fit and PHG/OC and ACC/caudate each interrelating age to GP and GP to AUDIT scores. These findings confirmed change in positive AE as a psychological mechanism mitigating alcohol misuse as individuals age and highlighted the neural processes of cue-reactivity interrelating age and alcohol use severity.

Neural cue reactivity is not stronger in male than in female patients with alcohol use disorder.

Background: Males consume more alcohol than females, and alcohol use disorder (AUD) is more prevalent in males than females. However, females progress faster to AUD. Sex differences in neural alcohol cue reactivity were previously observed in young social drinkers, indicating a role of hypersensitivity to alcohol-related cues in very early stages of addiction. To our knowledge, this is the first study on patients diagnosed with AUD to test sex differences in neural reactivity to alcohol cues in order to widen previous findings. Methods: We analyzed data from previous studies, using a well-established functional magnetic resonance imaging (fMRI) paradigm to compare neural reactivity to alcohol cues between 42 female and 124 male patients with AUD (mean age 45 and 46 years) in predefined regions of interest that were implicated by previous studies (ventral and dorsal striatum as well as caudate, putamen, amygdala, hippocampus, insula, anterior cingulate cortex, and medial prefrontal cortex) using independent samples t-tests. Post-hoc, effect size calculations were performed. Results: Throughout all nine regions of interest, we found no statistically significant sex differences in neural reactivity toward alcoholic pictures alone or in comparison to neutral pictures (p > 0.05, FDR-corrected). Post-hoc effect size estimates indicated a magnitude between 0.137 and 0.418 (Hedge's g) on alcohol reactivity to alcohol cues compared to neutral cues and indicate very small to less than medium effect sizes in the direction of higher cue reactivity in female patients. Conclusion: Previous studies showed sex differences in neural alcohol cue reactivity in younger social and problematic alcohol drinkers, i.e., stronger striatal cue-reactivity in males. After correction for multiple comparisons, we did not observe significant sex differences in a cohort of middle-aged females and males with AUD. Sex differences that are present during early phases of addiction development might disappear at later stages of AUD and might thus be considered as clinically less relevant in patients with more severe AUD.

"It's a beer!": Brain functional hyperconnectivity during processing of alcohol-related images in young binge drinkers.

Alcohol attentional bias has been pointed as a major marker of alcohol misuse. Recent evidence has revealed that brain functional connectivity (FC) may be a valuable index of the brain networks' integrity in young binge drinkers (BDs). However, there is no study to date examining the FC networks linked to the processing of alcohol-related images in this population. The present study aimed to explore the FC signatures underlying alcohol attention bias in young BDs. Thus, electroencephalographic (EEG) activity was recorded in 54 college students (55.5% females; 27 non/low-drinkers and 27 BDs) while performing a visual alcohol cue-reactivity task. We evaluated whole-brain FC profiles during the processing of alcoholic and non-alcoholic cues, as well as their potential relationship with craving and severity of alcohol use. Results showed that, at the behavioural level, BDs rated alcohol-related images as more pleasant/attractive than non/low-drinkers. Furthermore, at the electrophysiological level, BDs exhibited increased beta-band FC-particularly in the fronto-parieto-occipital network-when processing alcoholic cues. Conversely, they displayed reduced theta-band FC relatively to non/low-drinkers for non-alcoholic images. These hyper-/hypo-connectivity patterns were associated with higher alcohol craving levels. Findings are congruent with previous neurofunctional studies reporting an attentional bias towards alcohol-related information in BDs. These results may have important clinical implications as this neural reactivity to alcoholic cues may contribute to the maintenance and/or escalation of the drinking pattern. Finally, the present study constitutes the first evidence showing that FC networks may be a sensitive indicator to alcohol attentional bias in BDs.

Sex moderates effects of alcohol and cannabis co-use on alcohol and stress reactivity.

BACKGROUND: Simultaneous or concurrent use (co-use) of alcohol and cannabis is associated with greater use of both substances over time, academic difficulties, more severe substance use consequences, and adverse impacts on cognitive functioning than the use of a single substance or no substance use. This study examined potential neural mechanisms underlying co-use behaviors in comparison to single substance use. Specifically, we compared alcohol cue reactivity and stress-cue reactivity among individuals who reported frequent same-day co-use of alcohol and cannabis and individuals who reported only alcohol use. METHODS: The sample included 88 individuals (41 women) who reported only alcohol use and 24 individuals (8 women) who reported co-use of alcohol and cannabis on at least 50% of drinking occasions. All participants completed fMRI stress and alcohol cue reactivity tasks. Because of known sex effects on stress reactivity and alcohol cue reactivity, we tested sex by co-use interactions. RESULTS: During alcohol cue presentation, co-users had less activation in the thalamus and dorsomedial prefrontal cortex than alcohol-only users, effects that were driven by differences in responses to neutral cues. Examination of stress cue reactivity revealed sex by co-use interactions in the lingual gyrus, with women co-users showing a greater difference between negative and neutral cue reactivity than all other groups. In addition, women co-users had greater connectivity between the nucleus accumbens and both the medial orbitofrontal cortex and the rostral anterior cingulate cortex during negative cue presentation than the other groups. CONCLUSIONS: These results provide preliminary evidence of enhanced stress cue reactivity in individuals reporting co-use of alcohol and cannabis, particularly women co-users.

Test-retest reliability of neural alcohol cue-reactivity: Is there light at the end of the magnetic resonance imaging tube?

Over the last decades, the assessment of alcohol cue-reactivity gained popularity in addiction research, and efforts were undertaken to establish neural biomarkers. This attempt however depends on the reliability of cue-induced brain activation. Thus, we assessed test-retest reliability of alcohol cue-reactivity and its implications for imaging studies in addiction. We investigated test-retest reliability of alcohol cue-induced brain activation in 144 alcohol-dependent patients over 2 weeks. We computed established reliability estimates, such as intraclass correlation (ICC), Dice and Jaccard coefficients, for the three contrast conditions of interest: 'alcohol', 'neutral' and the 'alcohol versus neutral' difference contrast. We also investigated how test-retest reliability of the different contrasts affected the capacity to establishing associations with clinical data and determining effect size estimates. Whereas brain activation, indexed by the constituting contrast conditions 'alcohol' and 'neutral' separately, displayed overall moderate (ICC > 0.4) to good (ICC > 0.75) test-retest reliability in areas of the mesocorticolimbic system, the difference contrast 'alcohol versus neutral' showed poor overall reliability (ICC < 0.40), which was related to the intercorrelation between the constituting conditions. Data simulations and analyses of craving data confirmed that the low reliability of the difference contrast substantially limited the capacity to establish associations with clinical data and precisely estimate effect sizes. Future research on alcohol cue-reactivity should be cautioned by the low reliability of the common 'alcohol versus neutral' difference contrast. We propose that this limitation can be overcome by using the constituent task conditions as an individual difference measure, when intending to longitudinally monitor brain responses.

Transcranial direct current stimulation combined with alcohol cue inhibitory control training reduces the risk of early alcohol relapse: A randomized placebo-controlled clinical trial.

BACKGROUND: Approximately half of all people with alcohol use disorder (AUD) relapse into alcohol reuse in the next few weeks after a withdrawal treatment. Brain stimulation and cognitive training represent recent forms of complementary interventions in the context of AUD. OBJECTIVE: To evaluate the clinical efficacy of five sessions of 2 mA bilateral transcranial direct current stimulation (tDCS) for 20 min over the dorsolateral prefrontal cortex (DLPFC) (left cathodal/right anodal) combined with alcohol cue inhibitory control training (ICT) as part of rehabilitation. The secondary outcomes were executive functioning (e.g. response inhibition) and craving intensity, two mechanisms strongly related to abstinence. METHODS: A randomized clinical trial with patients (n = 125) with severe AUD at a withdrawal treatment unit. Each patient was randomly assigned to one of four conditions, in a 2 [verum vs. sham tDCS] x 2 [alcohol cue vs. neutral ICT] factorial design. The main outcome of treatment was the abstinence rate after two weeks or more (up to one year). RESULTS: Verum tDCS improved the abstinence rate at the 2-week follow-up compared to the sham condition, independently of the training condition (79.7% [95% CI = 69.8-89.6] vs. 60.7% [95% CI = 48.3-73.1]; p = .02). A priori contrasts analyses revealed higher abstinence rates for the verum tDCS associated with alcohol cue ICT (86.1% [31/36; 95% CI = 74.6-97.6]) than for the other three conditions (64% [57/89; 95% CI = 54-74]). These positive clinical effects on abstinence did not persist beyond two weeks after the intervention. Neither the reduction of craving nor the improvement in executive control resulted specifically from prefrontal-tDCS and ICT. CONCLUSIONS: AUD patients who received tDCS applied to DLPFC showed a significantly higher abstinence rate during the weeks following rehabilitation. When combined with alcohol specific ICT, brain stimulation may provide better clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov number NCT03447054 https://clinicaltrials.gov/ct2/show/NCT03447054.

Combined varenicline and naltrexone attenuates alcohol cue-elicited activation in heavy drinking smokers.

BACKGROUND: There is a strong bidirectional relationship between the use of alcohol and cigarettes which results in various challenges for treating those who co-use both substances. While varenicline and naltrexone each have FDA-approval for nicotine and alcohol use disorder, respectively, there is evidence that their clinical benefit may extend across the two disorders. Critically, the effect of combined varenicline and naltrexone on neural reactivity to alcohol cues among heavy drinking smokers has not yet been studied. Probing the effect of the combination therapy on alcohol cue-reactivity may give insight to the mechanisms underlying its efficacy. METHODS: Forty-seven heavy drinking smokers enrolled in two medication studies were randomized to receive varenicline alone (n = 11), varenicline plus naltrexone (n = 11), or placebo (n = 25). Participants completed an fMRI alcohol cue-reactivity task and rated their in-scanner alcohol craving. Whole-brain analyses examined the effect of medication on alcohol cue-elicited neural response. RESULTS: Varenicline plus naltrexone attenuated alcohol cue-elicited activation in mesolimbic regions relative to varenicline alone and to placebo (Z > 2.3, p < 0.05). The combination varenicline and naltrexone group also endorsed lower in-scanner alcohol craving relative to varenicline alone group (p = 0.04). CONCLUSIONS: These findings provide evidence for the benefit of combined therapy of varenicline and naltrexone over varenicline alone for the attenuation of alcohol cue-elicited neural activation. This study provides a preliminary proof-of-mechanism for this combination pharmacotherapy and suggests that naltrexone may be driving the reductions in cue-elicited alcohol craving in the brain. Further clinical studies using the combined therapy to treat heavy drinking smokers are warranted.

Nalmefene attenuates neural alcohol cue-reactivity in the ventral striatum and subjective alcohol craving in patients with alcohol use disorder.

RATIONALE: Alcohol use disorder is a common and devastating mental illness for which satisfactory treatments are still lacking. Nalmefene, as an opioid receptor modulator, could pharmacologically support the reduction of drinking by reducing the (anticipated) rewarding effects of alcohol and expanding the range of treatment options. It has been hypothesized that nalmefene acts via an indirect modulation of the mesolimbic reward system. So far, only a few imaging findings on the neuronal response to nalmefene are available. OBJECTIVES: We tested the effect of a single dose of 18 mg nalmefene on neuronal cue-reactivity in the ventral and dorsal striatum and subjective craving. METHODS: Eighteen non-treatment-seeking participants with alcohol use disorder (67% male, M = 50.3 ± 13.9 years) with a current high-risk drinking level (M = 76.9 ± 52 g of pure alcohol per day) were investigated using a cue-reactivity task during functional magnetic resonance imaging (fMRI) in a double-blind, placebo-controlled, cross-over study/design. In addition, self-reported craving was assessed before and after exposure to alcohol cues. RESULTS: An a priori defined region of interest (ROI) analysis of fMRI data from 15 participants revealed that nalmefene reduced alcohol cue-reactivity in the ventral, but not the dorsal striatum. Additionally, the subjective craving was significantly reduced after the cue-reactivity task under nalmefene compared to placebo. CONCLUSION: In the present study, reduced craving and cue-reactivity to alcohol stimuli in the ventral striatum by nalmefene indicates a potential anti-craving effect of this drug via attenuation of neural alcohol cue-reactivity.

Striatal alcohol cue-reactivity is stronger in male than female problem drinkers.

Despite apparent sex differences in the development and treatment of alcohol use disorder, relatively little is known about the underlying neural mechanisms. In this study, we therefore investigated neural cue-reactivity in a sample of male (n = 28) and female (n = 27) problem drinkers (matched on age and alcohol use severity) with an average alcohol use disorder identification test score of 12 which is indicative of a likely alcohol use disorder. Neural cue-reactivity data were extracted from four regions of interest: the ventral and dorsal striatum and the ventral and dorsal anterior cingulate cortex, with a significance level set at p < 0.05. While the cue-reactivity paradigm induced similar levels of self-reported craving in men and women, visual alcohol cues induced significantly stronger striatal activation in men compared to drinkers. While sex differences in ventral striatal cue-reactivity were partly explained by sex differences in alcohol intake, cannabis use, negative affect and anxiety, this was not the case for sex differences in dorsal striatal cue-reactivity. These results suggest that alcohol cues are differentially processed by men and women and that the neurobiological mechanisms behind cue-reactivity differ between the sexes. Consequently, paradigms using alcohol-related pictures may not be optimal to induce cue-reactivity in female drinkers and may not be optimal to measure neurobiological markers of alcohol use severity and relapse. Future alcohol cue-reactivity studies should, in addition to including both men and women, include different types of cues (e.g., stressors and imagery in addition to pictures) to assess sex differences in alcohol cue-reactivity.

An Examination of Behavioral and Neuronal Effects of Comorbid Traumatic Brain Injury and Alcohol Use.

BACKGROUND: Chronic alcohol use disorders (AUDs) and traumatic brain injury (TBI) are highly comorbid and share commonly affected neuronal substrates (i.e., prefrontal cortex, limbic system, and cerebellum). However, no studies have examined how combined physical trauma and heavy drinking affect neurocircuitry relative to heavy drinking alone. METHODS: The current study investigated whether comorbid AUDs and mild or moderate TBI (AUDs+TBI) would negatively affect maladaptive drinking behaviors (n = 90 AUDs+TBI; n = 62 AUDs) as well as brain structure (i.e., increased atrophy; n = 62 AUDs+TBI; n = 44 AUDs) and function (i.e., activation during gustatory cue reactivity; n = 55 AUDs+TBI; n = 37 AUDs) relative to AUDs alone. RESULTS: Participants reported a much higher incidence of trauma (59.2%) compared with the general population. There were no differences in demographic and clinical measures between groups, suggesting that they were well matched. Although maladaptive drinking behaviors tended to be worse for the AUDs+TBI group, effect sizes were small and not statistically significant. Increased alcohol-cue reactivity was observed in bilateral anterior insula and orbitofrontal cortex, anterior cingulate cortex, medial prefrontal cortex, posterior cingulate cortex, dorsal striatum, thalamus, brainstem, and cerebellum across both groups relative to a carefully matched appetitive control. However, there were no significant differences in structural integrity or functional activation between AUDs+TBI and AUDs participants, even when controlling for AUD severity. CONCLUSIONS: Current results indicate that a combined history of mild or moderate TBI was not sufficient to alter drinking behaviors and/or underlying neurocircuitry at detectable levels relative to heavy drinking alone. Future studies should examine the potential long-term effects of combined alcohol and trauma on brain functioning.

Prospective changes in neural alcohol cue reactivity in at-risk adolescents.

Adolescence represents an ideal time for elucidating the etiology of cue reactivity profiles. This study examined the influence of three risk factors consistently associated with heavy adolescent drinking on alcohol cue reactivity. Youth were first assessed while still naïve to alcohol (12-14 years old) and followed after transitioning into alcohol use (17-21 years old). The effects of family history of substance use disorder, sex, and history of early of dating (i.e., before 14 years of age) on BOLD response contrast to alcohol picture cues were examined in a linear mixed model, controlling for age and alcohol use patterns at follow-up. Activation to alcohol picture cues differed as a function of risk factor and time. At baseline, family history positive youth showed greater activation to alcohol cues than family history negative peers in the right middle occipital and anterior cingulate gyri. Youth with a history of early-dating showed greater activation to alcohol cues, compared to non-early daters, in the left anterior cingulate/white matter region. Girls showed greater activation to alcohol than boys at baseline in left middle frontal gyrus. At follow-up, after drinking started, patterns reversed for each risk factor. These results indicate that even prior to initiating alcohol use, adolescents showed differences in activation to alcohol cues based on their family history, dating history, and sex.

Postretrieval Extinction Attenuates Alcohol Cue Reactivity in Rats.

BACKGROUND: Conditioned responses to alcohol-associated cues can hinder recovery from alcohol use disorder (AUD). Cue exposure (extinction) therapy (CET) can reduce reactivity to alcohol cues, but its efficacy is limited by phenomena such as spontaneous recovery and reinstatement that can cause a return of conditioned responding after extinction. Using a preclinical model of alcohol cue reactivity in rats, we evaluated whether the efficacy of alcohol CET could be improved by conducting CET during the memory reconsolidation window after retrieval of cue-alcohol associations. METHODS: Rats were provided with intermittent access to unsweetened alcohol. Rats were then trained to predict alcohol access based on a visual cue. Next, rats were treated with either standard extinction (n = 14) or postretrieval extinction (n = 13). Rats were then tested for long-term memory of extinction and susceptibility to spontaneous recovery and reinstatement. RESULTS: Despite equivalent extinction, rats treated with postretrieval extinction exhibited reduced spontaneous recovery and reinstatement relative to rats treated with standard extinction. CONCLUSIONS: Postretrieval CET shows promise for persistently attenuating the risk to relapse posed by alcohol cues in individuals with AUD.

Alcohol-cue exposure decreases response inhibition towards alcohol-related stimuli in detoxified alcohol-dependent patients.

The induction of alcohol craving and the cognitive processing of alcohol-related stimuli in alcohol-dependent patients have been reported to compete with inhibitory control and contribute to alcohol relapse. The aim of the present study is to investigate whether the induction of a craving state, using an alcohol cue exposure paradigm, influences response inhibition towards both neutral stimuli and alcohol-related stimuli in alcohol-dependent patients. Thirty-one detoxified alcohol-dependent patients were exposed to either their preferred alcoholic beverage or to a glass of water. They then performed a modified stop signal task, which used alcohol-related words, neutral words and non-words, and a lexical decision as the Go response. The alcohol-cue exposure group reported significantly higher alcohol craving and showed higher percentages of commission errors towards alcohol-related words than the control group. All participants, but especially those of the alcohol-cue exposure group, showed also shorter reaction times when alcohol words were used as targets in go trials. The induction of alcohol craving in detoxified alcohol-dependent patients increases the motivational salience value of alcohol stimuli, leading them to automatically approach alcohol-related cues and therefore impairing response inhibition towards those stimuli.

Attentional bias toward alcohol-related stimuli in heavy drinkers: evidence from dynamic eye movement recording.

BACKGROUND: It has been proposed that attentional biases toward alcohol stimuli are contributing factors maintaining problematic drinking behavior. OBJECTIVE: The main goal of the present set of studies was to provide an examination of dynamic attentional mechanisms associated with alcohol consumption derived from eye movement monitoring. METHOD: Undergraduate students were recruited for two studies. In Experiment 1, 80 students were exposed to complex scenes (containing alcohol-related cues or not) viewed at a self-determined presentation rate. In Experiment 2, 80 students were exposed to the stimuli for a fixed presentation time and asked to memorize the photographs. In both studies, participants completed the Khavari Alcohol Test (KAT) to measure their drinking behaviors. RESULTS: Experiment 1 revealed that alcohol consumption was unrelated to eye movement measures on alcohol-related objects within pictures. However, results of Experiment 2 indicated that saccades into and out of the alcohol-related zones were more frequent as alcohol consumption increased. The time spent and the speed of the first fixation in the alcohol-related zone did not explain the variance in alcohol consumption. CONCLUSION: Attentional biases associated with alcohol consumption might be better understood in terms of dynamic attention mechanisms. More precisely, heavy drinker's attention seems to be constantly drawn back to alcohol-related objects once they are first fixated and when attention is enforced through other cognitive demands. From a clinical viewpoint, dynamic attentional biases might contribute to the development or maintenance of alcohol-related problems and this observation might help guide attention-based interventions.

The role of social stimuli content in neuroimaging studies investigating alcohol cue-reactivity.

INTRODUCTION: Cue-reactivity is thought to play a fundamental role in the maintenance of addiction. The incentive sensitization theory proposes that conditioned responses are related to increased sensitivity of the reward-related dopaminergic pathways in the brain. However, neuroimaging studies on alcohol cue-reactivity show inconsistent results. METHODS: Stimuli content of 26 alcohol cue-reactivity studies was systematically reviewed. RESULTS: No differences were found between alcoholic beverage stimuli and non-alcoholic beverage stimuli in human display and brand factors; however, alcoholic beverage stimuli were more likely to display social interaction compared to non-alcoholic beverage stimuli. CONCLUSIONS: Given that processing of social information activates brain areas that partly overlap with reward-related brain areas associated with cue-reactivity, such differences between conditions can introduce noise in the findings. We therefore suggest matching stimuli sets on the reviewed factors carefully to improve reliability of neuroimaging studies investigating alcohol-related cue-reactivity.

Association between alcohol-cue modulated startle reactions and drinking behaviour in alcohol dependent patients - results of the PREDICT study.

Previous research on alcohol dependent patients has shown that variations in eyeblink startle response can be used as an indicator of their emotional responses to alcohol-related stimuli. Postulating that reactions on substance associated stimuli are controlled by either a negative or a positive affective processing system, we expect that abstinent alcoholics react differently (within-group) in the emotional evaluation of alcohol cues. Furthermore, we assumed the startle response to covary with medication response to acamprosate and naltrexone. We measured 74 detoxified inpatients' acoustic startle responses while they were being presented with alcohol-related images as well as affectively negative, neutral, and positive pictures before they were randomized to pharmacotherapy. Group-mean startle peak amplitudes were lowest for alcohol-related cues. The relative startle response (alcohol cues set in relation to the other stimulus categories) did not correlate with craving for alcohol (OCDS) or alcohol cue induced self-ratings of arousal, valence and craving. Patients with a lower percentage of abstinent days in the 90 days prior to the last drinking day showed a lower ("more appetitive") startle response to alcohol cues. A survival analysis using the time to first heavy drinking day as the survival criterion revealed a significant interaction between alcohol-cue startle responses and medication type. The results indicate that the psycho-physiological measure of emotional evaluation of alcohol cues includes unconscious processing not reflected by conscious self-ratings. Furthermore, our result of a differential medication effect may encourage further studies to use biological characteristics to stratify patients as a step towards individualized treatment for alcohol dependence.

Social pressure-induced craving in patients with alcohol dependence: application of virtual reality to coping skill training.

OBJECTIVE: This study was conducted to assess the interaction between alcohol cues and social pressure in the induction of alcohol craving. METHODS: Fourteen male patients with alcohol dependence and 14 age-matched social drinkers completed a virtual reality coping skill training program composed of four blocks according to the presence of alcohol cues (x2) and social pressure (x2). Before and after each block, the craving levels were measured using a visual analogue scale. RESULTS: Patients with alcohol dependence reported extremely high levels of craving immediately upon exposure to a virtual environment with alcohol cues, regardless of social pressure. In contrast, the craving levels of social drinkers were influenced by social pressure from virtual avatars. CONCLUSION: Our findings imply that an alcohol cue-laden environment should interfere with the ability to use coping skills against social pressure in real-life situations.